Fluoride ingestion during tooth enamel development may result in enamel fluorosis. Mature fluorosed enamel has a decreased mineral content and an increased protein content as compared to normal enamel. The factor(s) responsible for causing these effects are largely unknown at present but may include a direct effect of fluoride on the developing ameloblasts. The objectives of this proposal are to investigate the effects of fluoride in altering ameloblast cell function. The specific aims of this proposal are to determine if chronic high fluoride ingestion alters: (1) the basic morphology of ameloblasts, and the timing of the phases in the life cycle of these cells; (2) the quantity of protein secreted into the forming enamel by ameloblasts; (3) the breakdown and removal of proteins from the developing enamel; (4) the secretion and activation of proteinases in early maturation stage enamel. Rats will be given drinking water containing either 0 or 100 ppm fluoride for 6 weeks. At the end of that time, the animals will be anesthetized and a sample of serum will be taken for fluoride analysis. Some animals will be either perfuse-fixed for morphological studies or injected with fluorochromes to study the timing of cellular modulation. In other studies, animals will be injected with either 35S-methionine to characterize secretion and degradation of enamel proteins or with 3H- glycine to investigate the formation and release of proteinases by ameloblasts. These studies are important in further investigating the mechanisms involved in the formation of enamel fluorosis.